Yun-Jin Lee

In vitro induction of differentiation by ginsenosides in F9 teratocarcinoma cells

The aim of this study was to determine the ability of the ginsenosides, extracts of Panax ginseng C.A. Meyer, to cause differentiation of F9 teratocarcinoma stem cells as a model system. F9 stem cells cultured in the presence of the ginsenosides together with dibutyryl cyclic AMP (dbcAMP) became parietal endoderm-like cells. Moreover, the expression of differentiation marker genes, such as laminin B1 and type IV collagen, was increased after treatment with the ginsenosides. Among the various purified ginsenosides, Rh1 and Rh2 were the most effective at causing differentiation of F9 cells. Since ginsenosides and glucocorticoid hormone have similar chemical structures, we examined the possibility of the involvement of a glucocorticoid receptor (GR) in the differentiation process induced by the ginsenosides. According to Southwestern blot analysis, a 94 kDa protein regarded as a GR was detected in F9 cells cultured in the medium containing the ginsenosides Rh1 or Rh2. In addition, F9 stem cells treated with the ginsenosides Rh1 or Rh2 and with RU486, a glucocorticoid antagonist with a high affinity for the GR, did not differentiate into endoderm cells morphologically, and the expression of laminin B1 gene was not induced in these cells. In a gel mobility shift assay, protein factors capable of binding to the glucocorticoid responsive element (GRE) specifically were detected in nuclear extracts of the ginsenoside-treated F9 cells. Moreover, overexpression of GR by cotransfection of GR expression vector and GRE-luciferase vector enhanced the transactivation activity of GRE promoter in the presence of ginsenosides Rh1 or Rh2 and was further augmented by dbcAMP. In addition, ginsenosides Rh1 and Rh2 bound to a GR assessed by whole-cell binding assay, even though the specific binding affinity was weaker compared to dexamethasone. Based on these data, we suggest that the ginsenosides Rh1 and Rh2 cause the differentiation of F9 cells and the effects of ginsenosides might be exerted via binding with a GR or its analogous nuclear receptor.

Clinico-radiological spectrum in enterovirus 71 infection involving the central nervous system in children

Enterovirus 71 infection causes hand, foot and mouth disease in children, and can produce diverse neurologic complications. Epidemics occurring in Korea between 2009 and 2012 resulted in the death of some patients. The present study aimed to clarify the correlation between clinical features and MRI findings in patients presenting with acute neurologic manifestations related to enterovirus 71 infection. Based on their clinical features, the patients were classified into four clinical groups: (1) brainstem encephalitis (n=17), characterized by myoclonus, tremor, ataxia, and autonomic dysregulation such as pulmonary hemorrhage; (2) aseptic meningitis (n=2); (3) encephalitis (n=2), characterized by decreased consciousness, seizure, and fever without myoclonus, tremor, ataxia, and autonomic dysregulation; and (4) acute flaccid paralysis (n=1). Thirteen of the 17 patients with brainstem encephalitis showed characteristic lesions in the dorsal brainstem and bilateral cerebellar dentate nuclei on brain MRI, whereas three had no abnormality. One of the two patients with meningitis had a small lesion in the left dorsal pons. Two patients with encephalitis had no apparent MRI abnormality. One patient with acute flaccid paralysis of the right leg had contrast-enhancement of the bilateral ventral nerve roots at the lumbar spine level on MRI. Five of 13 patients with lesions in the bilateral dentate nuclei of the cerebellum exhibited no cerebellar symptoms, while two with no cerebellar lesions developed ataxia. Although most patients presenting with neurologic manifestations of enterovirus 71 infection had characteristic clinical features together with typical MRI findings, the clinical features were not necessarily consistent with MRI findings.

Longitudinal Change of Vitamin D Status in Children With Epilepsy on Antiepileptic Drugs: Prevalence and Risk Factors

BACKGROUND Our aim was to evaluate the prevalence and risk factors of vitamin D deficiency and the changes of vitamin D level among children with epilepsy on antiepileptic drugs. METHODS The levels of serum 25-hydroxy vitamin D were measured at the start of antiepileptic drugs and at 6- to 12-month intervals in children with epilepsy taking antiepileptic drugs in Pusan National University Childrens Hospital. Vitamin D deficiency was defined as 25-hydroxy vitamin D levels <20 ng/mL and insufficiency between 21 and 29 ng/mL. RESULTS A total of 143 children (103 boys and 40 girls) with the mean age of 7.4 ± 5.4 years were included. The mean follow-up duration was 1.8 ± 0.8 years. At the start of antiepileptic drugs and the last follow-up, vitamin D deficiency or insufficiency was recognized in 56.6% (81 of 143) and 79.0% (113 of 143), respectively (P < 0.01). The mean value of initial 25-hydroxy vitamin D was 31.1 ± 14.7 ng/mL, which was significantly decreased to 20.2 ± 14.9 ng/mL (P < 0.01) in the last follow-up. Polytherapy (-16.0 ± 13.6 ng/mL), longer duration of ≥2 years (-23.5 ± 9.1 ng/mL), tube feeding (-18.2 ± 14.5 ng/mL), and overweight with body mass index of eighty-fifth percentile or greater (-17.0 ± 12.1 ng/mL) had a significant negative effect for the longitudinal change of 25-hydroxy vitamin D. Age, etiologies, seizure outcomes, and type of antiepileptic drugs (enzyme-inducing versus nonenzyme-inducing antiepileptic drugs) did not affect the longitudinal decrease of 25-hydroxy vitamin D. CONCLUSIONS A high proportion of these children on antiepileptic drugs had hypovitaminosis D and a significant decrease between the initial and the last follow-up. Polytherapy and longer duration of antiepileptic drugs, tube feeding, and overweight were independently associated with longitudinally significant decrease of 25-hydroxy vitamin D.

Optic Neuritis in Korean Children: Low Risk of Subsequent Multiple Sclerosis.

BACKGROUND A relationship between optic neuritis and multiple sclerosis has previously been reported in non-Asian adults. We extended the investigation to Korean children. OBJECTIVES We compared the clinical features, laboratory findings, and visual outcomes of optic neuritis between prepubertal children and postpubertal adolescents and evaluated the conversion rate of optic neuritis to multiple sclerosis in Korean children. METHODS We conducted a retrospective analysis of children less than 18 years of age presenting with optic neuritis at Pusan National University Hospital between January 2002 and December 2013. Outcomes and clinical, ophthalmologic, magnetic resonance imaging, and laboratory findings were reviewed. RESULTS Twenty-six children (male:female, 1:1.2) were included. Follow-up duration was 16.3 ± 27.5 months in the prepubertal children (≤10 years, n = 13) and 8.2 ± 9.2 months in postpubertal adolescent (>10 years, n = 13) (P = 0.32). There was no significant difference between the prepubertal group and postpubertal group in clinical, ophthalmologic, magnetic resonance imaging, or laboratory findings. Of two patients (7.7%) with abnormal brain magnetic resonance images, one developed multiple sclerosis and the other developed acute disseminated encephalomyelitis. Of three patients (11.5%) with relapsing optic neuritis, two developed systemic lupus erythematosus and one developed multiple sclerosis. CONCLUSION The risk of developing multiple sclerosis after pediatric optic neuritis was low (7.7%). Abnormal brain magnetic resonance imaging and relapsing optic neuritis should alert the clinician to systemic or neurological disorders.

Melkersson-Rosenthal Syndrome With Hashimoto Thyroiditis in a 9-Year-Old Girl: An Autoimmune Disorder

BACKGROUND Melkersson-Rosenthal syndrome (MRS) is a rare disorder of unknown cause. The classical triad of MRS is orofacial edema, recurrent facial paralysis, and a fissured tongue. PATIENT We present a 9-year-old girl with a recurrent peripheral facial paralysis. She experienced the first episode of a peripheral facial paralysis on the same side without orofacial swelling and lingua plicata 1 year ago. She was diagnosed with Hashimoto thyroiditis 9 months earlier, as confirmed by an endocrinologic investigation. RESULTS While the patient was hospitalized with recurrent facial paralysis, we found that serum levels of free thyroxine (1.3 ng/dL) and thyrotropin (0.4 uIU/mL) were within normal range, but the level of antithyroperoxidase antibodies (772.0 IU/mL) was very increased. She had been taking an oral prednisolone orally for 2 weeks. At the 1-month follow-up, the patients symptoms had completely disappeared. DISCUSSION The possible correlation between MRS and autoimmune disorders has been documented in only one report, which described an adult with autoimmune thyroiditis (Hashimoto thyroiditis) and MRS. We suggest that the co-occurrence of MRS and Hashimoto thyroiditis is not coincidental but linked to autoimmunity.

X-linked recessive myotubular myopathy with MTM1 mutations.

X-linked recessive myotubular myopathy (XLMTM) is a severe congenital muscle disorder caused by mutations in the MTM1 gene and characterized by severe hypotonia and generalized muscle weakness in affected males. It is generally a fatal disorder during the neonatal period and early infancy. The diagnosis is based on typical histopathological findings on muscle biopsy, combined with suggestive clinical features. We experienced a case of a newborn who required intubation and ventilator care because of profound hypotonia and respiratory difficulty. The preliminary diagnosis at the time of request for retrieval was hypoxic ischemic encephalopathy, but the infant was clinically reevaluated for generalized weakness and muscle atrophy. Muscle biopsies showed variability in fiber size and centrally located nuclei in nearly all the fibers. We detected an MTM1 gene mutation of c.1261-1C>A in the intron 10 region, and diagnosed the neonate with myotubular myopathy. The same mutation was detected in his mother.

Endovascular stenting of tracheoinnominate fistula after tracheostomy in a 14-year-old boy.

Tracheoinnominate artery fistula is a rare, fatal complication of tracheostomy, and prompt diagnosis and management are imperative. We report the case of tracheoinnominate artery fistula after tracheostomy in a 14-year-old boy with a history of severe periventricular leukomalacia, hydrocephalus, cerebral palsy, and epilepsy. The tracheoinnominate artery fistula was successfully treated with a stent graft insertion via the right common femoral artery. Endovascular repair of the tracheoinnominate artery fistula via stent grafting is a safe, effective, and minimally invasive treatment for patients in poor clinical conditions and is an alternative to traditional open surgical treatment.

Cerebrospinal fluid non-pleocytosis in pediatric enteroviral meningitis: Large-scale review

Lack of cerebrospinal fluid (CSF) pleocytosis has been reported in some children with enteroviral meningitis (EVM). The aim of this paper was to investigate the clinical spectrum and related factors in EVM with CSF non‐pleocytosis.

Comparison of conservative therapy and steroid therapy for Bell’s palsy in children

Purpose Bell’s palsy is characterized by sudden onset of unilateral facial weakness. The use of corticosteroids for childhood Bell’s palsy is controversial. This study aimed to identify clinical characteristics, etiology, and laboratory findings in childhood Bell’s palsy, and to evaluate the efficacy of corticosteroid treatment. Methods We conducted a retrospective analysis of children under 19 years of age treated for Bell’s palsy between January 2009 and June 2017, and followed up for over 1 month. Clinical characteristics, neuroimaging data, laboratory findings, treatments, and outcomes were reviewed. Patients with Bell’s palsy were divided into groups with (group 1) and without (group 2) corticosteroid treatment. Differences in onset age, sex, laterality, infection and vaccination history, degree of facial nerve palsy, and prognosis after treatment between the groups were analyzed. Results One hundred patients were included. Mean age at presentation was 7.4±5.62 years. A total of 73 patients (73%) received corticosteroids with or without intravenous antiviral agents, and 27 (27%) received only supportive treatment. There was no significant difference in the severity, laboratory findings, or neuroimaging findings between the groups. Significant improvement was observed in 68 (93.2%) and 26 patients (96.3%) in groups 1 and 2, respectively; this rate was not significantly different between the groups (P=0.48). Conclusion Childhood Bell’s palsy showed good prognosis with or without corticosteroid treatment; there was no difference in prognosis between treated and untreated groups. Steroid therapy in childhood Bell’s palsy may not significantly improve outcomes.

Comparison of Cerebrospinal Fluid Cytokine Levels in Children of Enteroviral Meningitis With Versus Without Pleocytosis

In viral meningitis, proinflammatory cytokines were detected at higher levels in the cerebrospinal fluid (CSF) and might play an important role in the inflammatory process. Our goal was to compare the cytokine profiles in the CSF of children of enteroviral meningitis (EVM) with versus without CSF pleocytosis. In total, 158 patients were enrolled in this prospective cohort study and were classified as EVM (group-A, n = 101), nonenteroviral aseptic meningitis (group-B, n = 27), and control (group-C, n = 30) groups. Of the 101 children with EVM, 71 had CSF pleocytosis (group-A1) and 30 had CSF nonpleocytosis (group-A2). Fifteen cytokines/chemokines in the CSF were measured simultaneously by immunoassay. Significant differences were found in interleukin (IL)-2, IL-6, and IL-8 levels in the CSF across the 3 groups, with the highest levels in group-A, followed by group-B and group-C. The levels of IL-1β, IL-2, IL-6, IL8, IL-10, interferon-γ, and tumor necrosis factor-α were significantly higher in the CSF of group-A1 than in that of group-A2. Group-A2 was significantly younger than group-A1 (3.4 ± 2.8 years versus 5.5 ± 3.2 years, P = 0.016). Significant differences between CSF pleocytosis and nonpleocytosis in EVM appear to be associated with distinct levels of CSF cytokines.